5-HT1C RECEPTOR-MEDIATED PHOSPHOINOSITIDE HYDROLYSIS IN THE RAT CHOROID-PLEXUS AFTER CHRONIC TREATMENT WITH CLOZAPINE

Chronic treatment with clozapine (14 days; 10 and 25 mg/kg/day) decrea ses 5-HT1C receptor density but not affinity in rat choroid plexus mea sured with [H-3]mesulergine. We now report the effects of the same clo zapine treatment regimens on the function of 5-HT1C receptors (measure d by maximal stimulation of 5-HT1C receptor-mediated phosphoinositide hydrolysis) in relation to receptor changes in rat choroid plexus. Qua ntitative 5-HT1C receptor autoradiography indicated that chronic cloza pine treatment decreased, in a dose-related manner, 5-HT1C receptor bi nding sites labeled by antagonist ([H-3]mesurergine) and agonist /-)-1 -(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, [I-125]DOI) radioligands . However, only the higher dose of clozapine decreased statistically s ignificantly the, maximal 5-HT1C receptor-mediated phosphoinositide hy drolysis response. Chronic administration of haloperidol (0.5 mg/kg/da y) did not change any of the 5-HT1C receptor parameters. In conclusion , chronic clozapine treatment is able to modulate the function of 5-HT 1C receptors. This further strengthens the possibility that 5-HT1C rec eptors may contribute to some of the atypical effects of clozapine.